Project Summary: Transient hyperglycemia in critically ill patients was once thought to be a benign consequence of physiologic stress, but recent studies have determined that hyperglycemia associated with critical illness is a strong and independent risk factor for increased morbidity and mortality in both adults and children. Further, studies in adults have documented that tight glycemic control with insulin via protocolized approaches improves clinical outcomes, including mortality, and glycemic control in critically ill adults has become standard of care at many institutions and is recommended by many medical advisory groups. Although data suggest that hyperglycemia is an independent risk factor for morbidity and mortality in critically ill children, there are no definitive studies examining outcome benefits of glycemic control in this population, and no published protocols to assist in the identification or treatment of hyperglycemia in this setting. Due to physiologic and disease differences, it is imprudent to translate adult approaches and findings to children. Prior to conducting multi-center clinical outcome studies on glycemic control in children, we believe the first step in this endeavor is to develop and validate a safe and effective approach to do so. Thus for over 3 years our group of pediatric intensivists and endocrinologists at Emory University has been studying this area. We have developed a physician-initiated, nurse-driven protocol to identify and treat patients with hyperglycemia in our high-acuity multidisciplinary pediatric critical care unit, and over the last 12 months we have internally evaluated this approach in our unit and have shown it to be safe and effective at controlling hyperglycemia. The objective in this project is to assemble a consortium of pediatric critical care centers of varying size, acuity, and composition and evaluate our glycemic control protocol on at least 250 children with hyperglycemia in different critical care units. The primary goal of this project is to externally validate our approach in terms of safety and ability to achieve and maintain steady and strict glycemic control in children with critical illness. At the conclusion of this 2 year study we will have (1) developed an externally validated, generalizable approach to control hyperglycemia in pediatric critical care patients, and (2) developed a consortium of interested centers for further study in this field. Therefore, we will have the requisite foundation to partake in the next step in this field and conduct a multi-center clinical outcome trial of glycemic control on pediatric critical illness.